19-17276539-T-C

Position:

• chr19-17276539-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014173.4(BABAM1):​c.614T>C​(p.Ile205Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BABAM1 NM_014173.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09

Genes affected

BABAM1 (HGNC:25008): (BRISC and BRCA1 A complex member 1) Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; positive regulation of DNA repair; and protein K63-linked deubiquitination. Located in cytosol and nuclear body. Part of BRCA1-A complex and BRISC complex. [provided by Alliance of Genome Resources, Apr 2022]

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.614T>C	p.Ile205Thr	missense_variant	7/9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.614T>C	p.Ile205Thr	missense_variant	7/9		NP_001028721.1
BABAM1	NM_001288756.2	c.614T>C	p.Ile205Thr	missense_variant	7/9		NP_001275685.1
BABAM1	NM_001288757.2	c.389T>C	p.Ile130Thr	missense_variant	4/6		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.614T>C	p.Ile205Thr	missense_variant	7/9	1	NM_014173.4	ENSP00000471605	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2023

The c.614T>C (p.I205T) alteration is located in exon 7 (coding exon 6) of the BABAM1 gene. This alteration results from a T to C substitution at nucleotide position 614, causing the isoleucine (I) at amino acid position 205 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.083	T;T;T;T;T;T;.;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D;.;D;D;.;D;D
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M;.;M;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-2.2	.;.;N;.;.;.;.;.
REVEL	Uncertain	0.32
Sift	Benign	0.045	.;.;D;.;.;.;.;.
Sift4G	Benign	0.23	T;T;T;T;D;T;D;D
Polyphen		0.78	P;.;P;P;.;.;.;.
Vest4		0.78
MutPred		0.47		Gain of glycosylation at I205 (P = 0.0034);.;Gain of glycosylation at I205 (P = 0.0034);Gain of glycosylation at I205 (P = 0.0034);.;.;.;Gain of glycosylation at I205 (P = 0.0034);
MVP		0.54
MPC		0.98
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17387348;